The Electron Microscopy Shared Facility in the University of New Mexico School of Medicine was established in 1966 and has been periodically upgraded by funds from the School of Medicine, the State of New Mexico and NIH/NCRR (SIG grants awarded in 1987 for scanning electron microscopy and image processing). The facility achieved substantial recognition in the late 1980s and early 1990s when key users published new methods to electrophoretically transfer macromolecular complexes from non-denaturing gels onto TEM grids in order to image interacting species within complex reactions ("snapshot blotting") and to map receptor distributions on cell surfaces by immunogold labeling and SEM imaging in the backscattered electron imaging mode. In the mid- 1990s, the pool of intensive EM users diminished as key investigators either retired or focused on other research technologies. This application was prepared in response to a recent (since 1998) strong resurgence of interest in TEM as a research tool among UNM investigators. The ten major and four minor users described here come from four different academic departments and participate in three different SOM research programs, Signal Transduction, Adhesion and Trafficking, Molecular Genetics and Molecular Virology, and Neurosciences. Nine of the 10 major investigators direct NIH-funded laboratories. These users have particularly established need for a TEM with features found only on the new generation of instruments, including computer-assisted alignment, increased contrast for improved imaging of small gold labels and a digital image acquisition system to facilitate image analysis and to increase sample throughput. These is also need for a new high vacuum evaporator with an electron gun for high resolution shadowing of macromolecular, viral and organelle structure. These features are available on the Hitachi H7500 TEM and Edwards high-vacuum evaporator requested here. The UNM School of Medicine and Cancer Research and Treatment Center have provided a matching commitment consisting of two years support for the service contract of the new TEM and two years of salary support for an experienced technician to serve as facilitator for new TEM studies by NIH-funded investigators. Funding for this application will significantly enhance research that integrates high quality electron microscopy into productive NIH-funded research programs in cellular and molecular biology and neurosciences at the University of New Mexico.